Action Points

This study found that adding bevacizumab (Avastin) to chemotherapy doesn't prolong life for seniors more than 65 with advanced non-small cell lung cancer (NSCLC).

Note that none of the propensity-adjusted models controlling for demographic and clinical characteristics showed any advantage to the addition of bevacizumab to carboplatin and paclitaxel chemotherapy for the Medicare population with advanced NSCLC.

Median survival was 9.7 months with the addition of bevacizumab to standard carboplatin (Paraplatin) and paclitaxel (Taxol) chemotherapy, compared with 8 to 8.9 months for carboplatin-paclitaxel alone, Deborah Schrag, MD, MPH, of the Dana Farber Cancer Institute in Boston, and colleagues reported in the April 18 issue of the Journal of the American Medical Association.

In their study of Medicare patients, the researchers found that the hazard ratios didn't even hint at benefit with the addition of bevacizumab when it was compared with carboplatin-paclitaxel use both after FDA approval of the bevacizumab combination (in 2006-2007) as well as before it was approved, in 2002-2005 (HR 1.01 and 0.93, P=0.85 and 0.28, respectively).

In the pivotal trial for approval, adding bevacizumab extended survival by 25%, to 12.3 months, from 10.3 months on standard chemotherapy alone. However, both a prior subgroup analysis of that trial and a meta-analysis with three others also failed to find a survival benefit for the 65-and-older population, which comprises two-thirds of all lung cancer diagnoses.

With these two lines of evidence from observational and clinical trial data, "bevacizumab should not be considered standard of care in this context," Schrag's group argued. "Clinicians should exercise caution in making treatment recommendations and should use bevacizumab judiciously for their older patients."

Some clinicians have already taken that tack despite CMS coverage, according to the results of the current trial.

"Adoption of bevacizumab was by no mean universal," Schrag noted at a press conference centered around the comparative effectiveness-themed issue of JAMA. "We didn't find that all physicians rushed out to administer this drug."

The study included 4,168 Medicare patients ages 65 and older with stage IIIB or IV non-squamous cell NSCLC diagnosed from 2002 to 2007 as recorded in the SEER (Surveillance, Epidemiology, and End Results) database.

Overall, only 7.6% (318 of 4,168) of the patients had received bevacizumab in the time frame after it was approved in 2006 to the end of the analysis in 2007.

Looking just at the patients diagnosed in 2006-2007, the proportion treated with the bevacizumab combination was relatively small at 21%. Even looking only at patients diagnosed in 2007, 22% received bevacizumab with standard chemotherapy.

Drugmaker Genentech acknowledged in a statement sent to reporters that seniors are typically underrepresented in the clinical trials used for regulatory submissions, but pointed out that even well-designed observational studies have limitations.

The company criticized Schrag's study for the small sample size with bevacizumab.

None of the propensity-adjusted models controlling for demographic and clinical characteristics showed any advantage to the addition of bevacizumab to carboplatin and paclitaxel chemotherapy for the Medicare population with advanced NSCLC.

Nor was a survival gain shown for the most advanced, stage IV patients. The bevacizumab combination didn't boost overall survival in that group compared with carboplatin-paclitaxel in 2006-2007 (HR 0.96, 95% confidence interval 0.83 to 1.12) or in 2002-2005 (HR 0.88, 95% CI, 0.77 to 1.02).

The researchers cautioned that their study lacked some essential clinical details, like performance status and baseline pulmonary function that might be used to select chemotherapy agents and could predict survival.

"However, the inability to identify patients with poor baseline lung function and limited performance status or other clinical contraindications to bevacizumab such as significant hemoptysis and brain metastases would be expected to widen rather than narrow the apparent gap in survival" between the treatment groups, the researchers noted.

The project was supported by the National Cancer Institute, and by a contract from the Agency for Healthcare Research and Quality as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program.

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